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Real-World Outcomes in Patients with Spinal Muscular Atrophy Treated with Onasemnogene Abeparvovec Monotherapy: Findings from the RESTORE Registry

Title: Real-World Outcomes in Patients with Spinal Muscular Atrophy Treated with Onasemnogene Abeparvovec Monotherapy: Findings from the RESTORE Registry
Authors: Servais, Laurent; Day, John W; De Vivo, Darryl C; Kirschner, Janbernd; Mercuri, Eugenio; Muntoni, Francesco; Proud, Crystal M; Shieh, Perry B; Tizzano, Eduardo F; Quijano-Roy, Susana; Desguerre, Isabelle; Saito, Kayoko; Faulkner, Eric; Benguerba, Kamal M; Raju, Dheeraj; LaMarca, Nicole; Sun, Rui; Anderson, Frederick A; Finkel, Richard S
Contributors: Surgery
Publication Year: 2026
Collection: University of Massachusetts, Medical School: eScholarship@UMMS
Subject Terms: AAV9 vector-based gene replacement therapy; RESTORE registry; long-term follow-up; motor neuron disease; newborn screening; onasemnogene abeparvovec; outcomes; rare disease; real-world evidence; spinal muscular atrophy
Description: BACKGROUND: Long-term, real-world effectiveness and safety data of disease-modifying treatments for spinal muscular atrophy (SMA) are important for assessing outcomes and providing information for a larger number and broader range of SMA patients than included in clinical trials. OBJECTIVE: We sought to describe patients with SMA treated with onasemnogene abeparvovec monotherapy in the real-world setting. METHODS: RESTORE is a prospective, multicenter, multinational, observational registry that captures data from a variety of sources. RESULTS: Recruitment started in September 2018. As of May 23, 2022, data were available for 168 patients treated with onasemnogene abeparvovec monotherapy. Median (IQR) age at initial SMA diagnosis was 1 (0-6) month and at onasemnogene abeparvovec infusion was 3 (1-10) months. Eighty patients (47.6%) had two and 70 (41.7%) had three copies of SMN2, and 98 (58.3%) were identified by newborn screening. Infants identified by newborn screening had a lower age at final assessment (mean age 11.5 months) and greater mean final (SD) CHOP INTEND score (57.0 [10.0] points) compared with clinically diagnosed patients (23.1 months; 52.1 [8.0] points). All patients maintained/achieved motor milestones. 48.5% (n = 81/167) experienced at least one treatment-emergent adverse event (AE), and 31/167 patients (18.6%) experienced at least one serious AE, of which 8/31 were considered treatment-related. CONCLUSION: These real-world outcomes support findings from the interventional trial program and demonstrate effectiveness of onasemnogene abeparvovec over a large patient population, which was consistent with initial clinical data and published 5-year follow-up data. Observed AEs were consistent with the established safety profile of onasemnogene abeparvovec. ; No embargo
Document Type: article in journal/newspaper
File Description: application/pdf
Language: unknown
Relation: Journal of Neuromuscular Diseases; https://doi.org/10.3233/jnd-230122; https://hdl.handle.net/20.500.14038/55112
DOI: 10.3233/JND-230122
Availability: https://doi.org/10.3233/JND-230122; https://hdl.handle.net/20.500.14038/55112
Rights: © 2024 – The authors. Published by IOS Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (CC BY-NC 4.0). ; http://creativecommons.org/licenses/by-nc/4.0/
Accession Number: edsbas.CF6F9F93
Database: BASE